SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03924050

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of Pemetrexed + Platinum Chemotherapy With or Without Toripalimab (JS001) in Advanced Non-small Cell Lung Cancer (NSCLC) Participants With TKI-resistant EGFR-mutated Tumors

This is a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with chemotherapyin Advanced Non-small Cell Lung Cancer (NSCLC) Participants with TKI-resistant EGFR-mutated Tumors; and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population. About 350 subjects with advanced non-small cell lung cancer with activated EGFR mutation will be 1:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors: The history of the previous lines of EGFR-TKI treament ( 1st or 2nd line of TKI vs. 3rd line of TKI vs. 1st or 2nd line of TKI + 3rd line of TKI) ; Disease stage (IIIB-C vs. IV);

NCT03924050 Non-small Cell Lung Cancer
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

1 Interventions

Name: TORIPALIMAB INJECTION(JS001 )

Description: TORIPALIMAB INJECTION(JS001 ) or Placebo, 240mg/6ml/vial, Q3W,up to 2 years of treatment.

Type: Drug

Group TORIPALIMAB combined with standard chemotherapy Group Placebo combined with standard chemotherapy


Primary Outcomes

Description: Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1)

Measure: PFS (Progression Free Survival) by investigator

Time: Approximately 2 years

Secondary Outcomes

Description: PFS evaluated by the Blinded Individual Review Committee (BIRC) based on RECIST1.1 criteria;

Measure: PFS (Progression Free Survival) by IRC (Independent Review Board)

Time: Approximately 2 years

Description: Objective response rate (ORR) evaluated by investigators and BIRC based on RECIST1.1;

Measure: ORR (Objective Response Rate)

Time: Approximately 2 years

Description: Duration of response (DOR) evaluated by investigators and BIRC based on RECIST1.1;

Measure: DOR (Duration of Response)

Time: Approximately 2 years

Description: Disease control rate (DCR) evaluated by investigators and BIRC based on RECIST1.1;

Measure: DCR (Disease of Response)

Time: Approximately 2 years

Description: Time to response (TTR) evaluated by investigators and BIRC based on RECIST1.1;

Measure: TTR (Time to Response)

Time: Approximately 2 years

Description: Overall survival (OS);

Measure: OS (Overall Survival) OS OS

Time: Approximately 2 years

Description: Adverse events (AEs) study drug related; serious adverse events (SAEs)study drug related; abnormal value of Lab test according to NCI-CTCAE V5.0

Measure: Incidence of AEs/SAEs

Time: Approximately 2 years

Purpose: Treatment

Allocation: Randomized

Sequential Assignment


There is one SNP

SNPs


1 T790M

Inclusion Criteria: - Only the patients meeting all the following criteria can be eligible to participate in the trial: - Fully informed consent and signed ICF; - Age of 18-75 years; - Histologically and/or cytologically confirmed advanced or recurrent stage III B-C or IV (AJCC Version 8) NSCLC with TKI-resistant EGFR-mutated tumors, which also satisfy following conditions: Without T790M mutation in exon 20 after 1st or 2nd generation EGFR-TKI (eg, gefitinib, erlotinib, icotinib, afatinib,etc.) --- T790M ---

treatment failure;If with T790M mutation in exon 20 after 1st or 2nd generation EGFR-TKI (eg, gefitinib, erlotinib, icotinib, afatinib,etc.),participants --- T790M ---

are required to have osimertinib or other 3rd generation EGFR-TKI treatment failure prior to enrollment.Participants with osimertinib treatment failure as 1st line therapy (regardless of their EGFR T790M mutation status);Previous neoadjuvant/adjuvant chemotherapy is allowed, but the time interval between the last dose of chemotherapy and recurrence/metastasis must be at least 6 months. --- T790M ---

- With at least one measurable disease per RECIST 1.1; - Agree to provide formalin fixed tumor specimen after EGFR-TKI treatment failure or provide fresh biopsy tissue; - ECOG performance status of 0-1; - Life expectancy ≥ 3 months; - Good organ function; - Any adverse event resulting from prior treatment, surgery, or radiotherapy must return to grade 0 or 1 according to NCI-CTCAE v5.0, except for alopecia of any grade; - Willing and able to follow protocol visits, treatment plans, laboratory tests and other study procedures; - Women of childbearing potential must have negative serum pregnancy test within 3 days prior to the first dose of investigational product: Exclusion Criteria: - Exclusion of tumor histology or cytology confirmed the presence of small cell lung cancer components, or squamous cell carcinoma components of more than 10%; - Combined with other driver mutations with known therapeutic drug, including but not limited to: ALK rearrangement, ROS1 mutation, BRAF600E mutation, and KRAS mutation; - Previous systematic chemotherapy for advanced NSCLC; - Subjects with no measurable lesions; - Subjects with cancer meningitis and spinal cord compression; - Subjects with untreated central nervous system (CNS) tumor metastasis; - Subjects were previously treated with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 agent; - Subjects with any active, known or suspected autoimmune disease; - Subjects who are now participating in other clinical studies or the last dose of prior investigational drug was given in < 4 weeks (or 5 half-lives) from the first investigational product administration of this study; - Subjects who were expected to receive any other antitumor therapy (eg, other maintenance therapy for NSCLC, radiotherapy, and/or surgical excision); - Subjects who received major surgery within 4 weeks prior to enrollment or were not fully recovered from prior surgery; - Subjects with other malignancies requiring concurrent treatment; - Subjects with grade II or above myocardial ischemia or myocardial infarction, or subjects with arrhythmia with poor control; - Subjects with uncontrolled pleural/pericardial effusion, or with ascites requiring repeated drainage; - Subjects with uncontrolled tumor-related pain; - Subjects with severe allergic reactions to other monoclonal antibodies and subjects with severe allergic reactions to pemetrexed, platinum or its prophylaxis; - Subjects with psychological disorder, alcohol alcoholism, drug abuse or drug dependency Inclusion Criteria: - Only the patients meeting all the following criteria can be eligible to participate in the trial: - Fully informed consent and signed ICF; - Age of 18-75 years; - Histologically and/or cytologically confirmed advanced or recurrent stage III B-C or IV (AJCC Version 8) NSCLC with TKI-resistant EGFR-mutated tumors, which also satisfy following conditions: Without T790M mutation in exon 20 after 1st or 2nd generation EGFR-TKI (eg, gefitinib, erlotinib, icotinib, afatinib,etc.) --- T790M ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1